Challenges in the management of localized Ewing sarcoma in a developing country

Abstract

Survival in pediatric Ewing sarcoma (ES) lags in low- and middle-income countries (LMICs). This study analyzed factors contributing to a lower outcome in an LMIC center. A retrospective case review of children with localized ES treated from January 2011 till December 2017 was performed. Neoadjuvant chemotherapy with alternating cycles of vincristine, doxorubicin, cyclophosphamide; and ifosfamide, etoposide was administered 3-weekly for 48 weeks. Reassessment was planned for week 12, followed by local therapy (surgery/radiotherapy or both) tailed by adjuvant chemotherapy. Forty-eight patients with mean age 8 years (range: 0.7–14) were evaluated. Extremity and central axis tumors were seen in 25 (52%) and 23 (48%) patients. Three patients died of neutropenic sepsis and five abandoned therapy. Local therapy included primary surgery, radiotherapy and a combination of surgery and radiotherapy in 7 (16%), 20 (45%) and 17 (39%) patients. The 3-year event-free survival (EFS) and disease-free survival (DFS) for the cohort were 47.7?±?11% and 57.6?±?11.2%. Time to local therapy >16 weeks was associated with inferior DFS vs. local therapy administered within 16 weeks [46.6?±?12.4 vs. 63.9?±?19.4, p=.046]. Older age, axial site, large size and incomplete surgical resection did not predict relapse/progression. Patients who received wide local excision, as local therapy, had 100% DFS. Coordinated efforts to ensure timely therapy can improve outcome in pediatric ES. Abandonment and treatment-related mortality (TRM) are additional challenges that need to be tackled in LMICs.     

手术联合化疗及放疗治疗儿童中枢性原始神经外胚瘤的疗效及预后分析

目的 分析手术联合化疗及放疗治疗儿童中枢性原始神经外胚瘤（cPNET）的疗效，并对其预后危险因素进行探讨。方法 收集2012年6月至2018年9月诊断为cPNET的42例患儿的临床资料并进行回顾性分析。结果 42例患儿的中位总生存（OS）期为2.0年，中位无事件生存（EFS）期为1.3年；1、3、5年OS率分别为76.2%±6.6%、41.4%±8.7%、37.3%±8.8%，1、3、5年EFS率分别为64.3%±7.4%、32.7%±8.0%、28.0%±8.1%。单因素分析结果显示，不同手术切除方式、化疗次数、危险度分级患儿OS率、EFS率比较差异均有统计学意义（P < 0.05），是否放疗患儿的OS率比较差异亦有统计学意义（P < 0.05）。多因素Cox回归分析结果显示，化疗次数、危险度分级是cPNET患儿OS率及EFS率的独立影响因素（P < 0.05），化疗次数越多，危险度越低，EFS率及OS率越高。结论 手术、化疗及放疗联合的综合治疗是目前治疗儿童cPNET的有效方法，早期发现早期治疗及尽量延长、坚持化疗有助于提高EFS率及OS率。     

Nonmetastatic pelvic Ewing sarcoma: report of the French society of pediatric oncology.

BACKGROUND: Since January, 1984, 59 children with histologically confirmed Ewing sarcoma of the pelvic bone have been treated with three successive chemotherapy protocols recommended by the French Society of Pediatric Oncology. The purpose of the current study was to evaluate the role of surgery and/or radiotherapy in local progression-free, disease-free, and overall survivals (LPFS, DFS, and OS, respectively). PROCEDURE: We retrospectively examined 59 children treated for nonmetastatic, pelvic Ewing sarcoma over the last 12 years. All were first treated with chemotherapy according to the current French protocol. Six patients developed progressive disease before local treatment and were excluded for local control and survival analysis. Local treatment was surgery alone in 17 cases, radiation therapy in 27 cases, and surgery plus radiation therapy in 9 cases. RESULTS: With a median of follow-up of 6.5 years, no significant differences in local control or survival were observed with the three chemotherapeutic protocols. Of the 53 patients evaluable for local control, 6 relapsed locally only, 8 had local and distant relapses, and 9 had distant metastases only. The 5-year OS rate was worst for patients with radiotherapy alone compared to those with surgery or combined modality treatment (44 % vs. 72 %, P = 0.043). The 5-year LPFS and DFS rates were worst in the radiotherapy-alone group but not significantly (63% vs. 79%, P = 0. 22 and 42% vs 71%, P =0.07, respectively). The importance of surgery to OS and DFS was confirmed by multivariate analysis (P = 0.026 and P = 0.048, respectively). One surviving patient was diagnosed with in-field fibrosarcoma, which was presumably radiation induced. CONCLUSIONS: Despite intensive, multiagent chemotherapy, survival from pelvic Ewing sarcoma has not improved over the past decade; however, the survival rate does not seem to be worse than that from Ewing sarcoma at other locations, insofar as at least 50% of the patients were cured. Surgery or a combination of surgery and radiation therapy are the best local treatment; exclusive radiation therapy should be reserved for patients with inoperable lesions or partially or nonchemosensitive tumors or when surgery would be an amputation.     

Does consolidation with autologous stem cell transplantation improve the outcome of children with metastatic or relapsed Ewing sarcoma?

OBJECTIVE: To evaluate the role of high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) as consolidation therapy for children with high-risk Ewing sarcoma (ES) treated at The Hospital for Sick Children (SickKids), Toronto. PATIENTS AND METHODS: The charts of children treated for high-risk ES (defined as metastatic at diagnosis or relapsed) between 1990 and 2005 at SickKids were reviewed. Forty-five children were identified. Twenty patients received ASCT after induction with vincristine, doxorubicin, ifosfamide, cyclophosphamide, and etoposide. Patients with resectable tumor or lung metastases underwent surgery and those with non-resectable tumors were treated with irradiation. Twenty-five patients were treated with conventional chemotherapy (CC). Primary metastatic patients were treated with either a local protocol or as per POG 9354. At relapse, patients were treated with topotecan, cyclophosphamide, then ifosfamide, carboplatin, and etoposide (ICE). Local control was attained with surgery and/or irradiation. RESULTS: Ten of the 20 patients treated with ASCT are alive (median follow-up 6 years), with 8/10 being in remission more than 5 years from diagnosis. The 3-year overall survival (OS) for ASCT was 59%, (95% CI: 36%, 81%) compared to 34% (14%, 53%) for patients treated with CC (P-value = 0.06). The 3-year event-free survival (EFS) for the ASCT was 39% (17%, 60%) compared to 32% (13%, 50%) in the CC group (P = 0.08). CONCLUSION: ASCT appears to add some benefit to conventional multimodality therapy for children with high-risk ES. Randomized controlled trials are warranted.     

Sparing strategy does not compromise prognosis in pediatric localized synovial sarcoma: experience of the International Society of Pediatric Oncology, Malignant Mesenchymal Tumors (SIOP-MMT) Working Group

Background

The aim of this analysis was to identify if the modified indications of radiotherapy (RT) or radical surgery compromised survival in pediatric synovial sarcoma (SS).

Procedure

Children with non‐metastatic SS, prospectively enrolled in three trials, were analyzed. After primary surgery or biopsy, they received chemotherapy. RT was planned after chemotherapy in patients who had not achieved a complete response (CR). The considered outcome was 5‐year overall survival (OS) and event‐free survival (EFS).

Results

Eighty‐eight patients were identified. Primary tumors were mainly located in limbs (66%). The first‐line therapy for 65 patients was primary resection. Of the 49 patients who had gross tumor resection, 43 received adjuvant chemotherapy, and 8 had RT. All of the 39 patients with macroscopic residual disease received chemotherapy, then only surgery (n = 12) ± RT (n = 22). The 5‐year EFS and OS rates were 68% and 85%, respectively. The TNM stage was a prognostic factor for relapse, whereas primary site of the tumor and TNM stage were prognostic factors for death.

Conclusions

Only 32% of survivors received RT. OS was similar to published data. Omission of RT may be considered in younger children, to limit the potential sequelae in patients with tumors less than 5 cm in size initially submitted to marginal resection. This strategy may also be considered in initially unresected cases, when the tumor is resected at delayed surgery with microscopically free margins, and in patients in complete remission after primary chemotherapy. Pediatr Blood Cancer 2011; 57: 1130–1136. © 2011 Wiley Periodicals, Inc.     

血清血管内皮生长因子/内皮抑素比值与儿童急性白血病的相关性

目的：检测急性白血病（AL）患儿血清血管内皮生长因子（VEGF）、内皮抑素（ES）水平,探讨VEGF /ES (V/E) 比值与儿童AL的临床相关性。方法：采用酶联免疫双抗体夹心法检测35例AL患儿化疗前后血清VEGF、ES水平及V/E比值,并与30例健康儿童进行比较。结果：化疗前AL患儿血清中VEGF和ES水平分别为196±66 pg/mL和 31±7 ng/mL,显著高于对照组（29±10 pg/mL、19±4 ng/mL; P0.05）。35例AL患儿化疗前血清VEGF、V/E 比值与骨髓白血病细胞数呈正相关 (r=0.301和0.411,P<0.05)。结论：血清VEGF和ES与儿童AL的发生发展有关,V/E比值能更准确反映AL患儿疾病动态变化情况,有利于指导相关治疗。     

Rex术后再发生上消化道出血的治疗策略探讨

目的 探讨小儿肝外门静脉高压Rex术后再发生上消化道出血时的治疗策略.方法 回顾性分析2008年6月至2017年1月126例门静脉海绵样变行Rex手术治疗患儿中,26例Rex术后再次出现呕血、黑便等上消化道出血表现患儿的临床资料.其中,113例患儿门静脉血管超声和CT显示未见明显分流血管,10例分流血管明显狭窄,3例门静脉血管超声可见分流血管通畅.21例患儿行上消化道造影检查,其中20例食管静脉曲张.采用输血止血等保守治疗10例.行Warren术治疗5例,其中1例先行Rex术治疗失败后改行Warren术.行Rex术治疗8例,其中1例失败,最终行Warren术治疗;1例先行内镜下硬化剂治疗后再出血,改行Rex术治疗.行肠系膜下静脉间置、门静脉主干-门静脉右支分流术1例.1例吻合口狭窄患儿行吻合口扩大成形术.行内镜下硬化剂治疗3例,1例术后再次出血后行Rex术治疗.所有患儿定期随访及复查.结果 行Rex术、Warren术和保守治疗患儿上消化道出血复发率分别为62.5％ (5/8)、20％(1/5)和90％(9/10),食道胃底静脉曲张率分别为75％(6/8)、20％(1/5)和100％,均以行Warren术患儿最低,三组比较,差异均有统计学意义(P=0.027和0.015).比较行Rex术、Warren术和保守治疗患儿术后随访时间[(22.9±24.4)个月、(26.6±24.1)个月和(26.0±20.4)个月],三组差异无统计学意义(P=0.939).行Rex术和Warren术患儿术后分流血管通畅率分别为62.5％(5/8)和100％,组间差异无统计学意义(P=0.118).保守治疗10例,其中1例分流血管通畅者迄今随访43个月未再出血,其余患儿均出现呕血或黑便.接受内镜下硬化剂治疗3例,其中1例分流血管闭锁者术后再次呕血行Rex手术治疗.结论 Warren术是治疗Rex术后复发的有效手术方法.保守治疗及内镜下硬化剂治疗仅适用于分流血管通畅的患儿,对于分流血管狭窄或闭锁的患儿应积极手术治疗.     

High-dose chemotherapy and autologous stem cell rescue in children with newly diagnosed high-risk or relapsed medulloblastoma or supratentorial primitive neuroectodermal tumor

BACKGROUND: Single or tandem double high-dose chemotherapy (HDCT) was used to treat children with newly diagnosed high-risk or relapsed medulloblastoma and supratentorial primitive neuroectodermal tumor (MB/sPNET) in order to defer or avoid radiotherapy in young children. PROCEDURE: Thirty-seven HDCTs were given to 25 children with newly diagnosed high-risk or relapsed MB/sPNET. Tandem double HDCT was used for 12 of 15 patients initially intended to receive double HDCT. RESULTS: Three-year EFS (+/-SE) in 6 newly diagnosed high-risk (>3 years old), 8 newly diagnosed (<3 years old), and 11 relapsed MB/sPNET was 83.3 +/- 15.2%, 62.5 +/- 20.5%, and 29.1 +/- 15.7%, respectively. Three-year EFS for patients in CR or PR and in less than PR at first HDCT was 67.4 +/- 11.0% and 16.7 +/- 15.2%, respectively (P = 0.001). Three-year EFS in patients initially intended to receive double HDCT and single HDCT was 66.0 +/- 12.4% and 40.0 +/- 15.5%, respectively. For 19 patients in CR or PR at first HDCT, 3-year EFS was 88.9 +/- 10.5% in tandem double HDCT group, and 44.4 +/- 16.6% in single HDCT group, respectively (P = 0.037). Although four treatment-related mortalities (TRMs) occurred during 25 first HDCTs, no TRM occurred during 12 second HDCTs. In four of eight young children, craniospinal radiotherapy was successfully withheld without subsequent relapse. CONCLUSIONS: High-dose chemotherapy may improve the survival of children with newly diagnosed high-risk MB/sPNET, and, to some extent, the survival of those with relapsed MB/sPNET. Further study is necessary to elucidate the efficacy of tandem double HDCT.     

Malignant peripheral nerve sheath tumors in children: a single-institution twenty-year experience

A retrospective series of pediatric patients with localized malignant peripheral nerve sheath tumors (MPNST) treated during a 20-year period at one institution is reported. Between 1976 and 1996, 24 consecutive children were treated by a multimodality approach. Conservative surgery was the treatment of choice: primary radical surgery was performed in 10. Postoperative radiotherapy was administered in 12 and adjuvant chemotherapy in 19. Eight patients were alive without evidence of disease, six in first complete remission and two in second complete remission, after a median follow-up of 230 months. The 10-year event-free survival (EFS) and survival were 29% and 41%, respectively. Survival was 80% for the patients who underwent radical surgery, and 14% for the others; 71% for patients with tumors smaller than 5 cm, and 29% for those with tumors 5 cm or larger. Local recurrence was the major cause for treatment failure (13 of 17; 76%); the rate of local relapse was 33% v 75% in patients who either received or did not receive radiotherapy. Complete surgical excision remains the most effective treatment for MPNST and represents the main prognostic factor along with tumor size. Radiotherapy seems to play a role in achieving local control, whereas the role of chemotherapy is uncertain.     

Interstitial brachytherapy for childhood soft tissue sarcoma

BACKGROUND: To evaluate the efficacy of interstitial brachytherapy (BRT) in children undergoing combined modality treatment for soft tissue sarcomas (STS). PROCEDURE: From September 1984 to December 2003, 50 children (median age 13 years, range 1 to 18) with STS who received BRT as part of loco-regional treatment were included. There were 30 males and 20 females, the majority (68%) had primary lesions, synovial sarcoma (32%) was the most common histological type, and 26% had high-grade lesions. Treatment included wide local excision and BRT with or without external beam radiotherapy (EBRT). Thirty children (60%) received BRT alone. RESULTS: After a median follow-up of 51 months, the local control (LC), disease-free survival, and overall survival were 82%, 68%, and 71%, respectively. LC was superior in patients with tumor size 5 cm (96% vs. 67%, P = 0.04), symptom duration <2 months versus >2 months (100% vs. 73%, P = 0.05), and Grade I versus Grade II versus Grade III tumors (100% vs. 93% vs. 57%, P = 0.03). Children receiving a combination of BRT and EBRT had comparable LC to those receiving BRT alone (78% vs. 84%, P = 0.89). There was no significant difference in LC for patients receiving LDR versus HDR BRT (77% vs. 92%, P = 0.32, for BRT alone; and 67% vs. 100%, P = 0.17, for BRT + EBRT). CONCLUSION: Interstitial BRT with or without EBRT appears to result in satisfactory outcome in children with STS. Radical BRT alone, when used judiciously in select groups of children, results in excellent local control and functional outcome with reduced treatment-related morbidity.     

A multi-institutional retrospective study of intracranial ependymoma in children: identification of risk factors.

PURPOSE: The goal of this multi-institutional retrospective study of children with intracranial ependymoma was to identify risk factors associated with unfavorable overall survival (OS) and event-free survival (EFS). PATIENTS AND METHODS: Clinical data, including demographics, tumor location, spread, histology, details of surgery, radiation treatment, and chemotherapy were collected. Clinical characteristics and univariate and multivariate analyses of risk factors for OS and EFS are presented. RESULTS: Eleven U.S. institutions contributed 83 patients treated from 1987 to 1991. The OS at 5 and 7 years was 57% and 46%, and EFS at 5 and 7 years was 42% and 33%. Patients 3 years of age or younger differed from the older group by more common infratentorial location, less common gross total resection (GTR), and postoperative use of chemotherapy rather than radiation. This younger group of patients had worse survival (P < 0.01) than the older age group. Other than young age, less than GTR and World Health Organization (WHO) II grade 3 histology were significant adverse risk factors for EFS in univariate and multivariate analyses. OS shared the same adverse risk factors except for histology in multivariate analysis, which was only of borderline significance (P = 0.05). Progression at the original tumor location, present in 89% of patients, was the major pattern of tumor recurrence. Adjuvant chemotherapy in the group older than 3 years or craniospinal radiation in M0 patients did not significantly change EFS. CONCLUSIONS: Adverse outcome in childhood intracranial ependymoma is related to age (3 years or younger), histology (grade 3), and degree of surgical resection (less than GTR). New approaches, particularly for local tumor control in younger patients, are needed to improve survival.     

Treatment of pediatric Hodgkin disease avoiding radiotherapy: excellent outcome with the Rotterdam-HD-84-protocol

BACKGROUND: To reduce radiotherapy (XRT) induced toxicity of treatment of children with Hodgkin disease (HD) while maintaining a high cure rate, we introduced a risk-adapted protocol consisting of chemotherapy (CT) alone in 1984. PROCEDURE: The outcome of 46 children treated for HD from 1984 until 2000 according to the Rotterdam-HD-84-protocol was determined. Children with stage I-IIA disease (n = 23), were treated with six courses of epirubicin, bleomycin, vinblastine, and dacarbazine (EBVD). Children with stage IIB-IV disease (n = 23), were treated with three to five alternating cycles of EBVD and mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). RESULTS: At a median follow-up time of 8.6 years (range 2.6-18.3 years), the 10-year overall survival (OS) is 95% and the event-free survival (EFS) 91%. In 5/46 patients XRT was administered because of residual mediastinal mass. Four children relapsed, two of them died. Up until now only one patient developed hypothyroidism; no symptomatic cardiac or pulmonary dysfunction, no second malignancy has been diagnosed. CONCLUSIONS: Risk-adapted treatment consisting of CT alone is highly efficacious for children with HD and toxicity is low. XRT was administered in only a small minority of children with HD. CT should be the first choice for HD in children and XRT should preferably be used for those with refractory or histologically proven residual disease or relapse.     

Multimodal therapy for the treatment of nonmetastatic Ewing sarcoma of pelvis

The purpose of this study was to evaluate the outcome of patients with Ewing sarcoma (ES) of the pelvis, attempting to identify prognostic factors to select patients for more aggressive treatment. Seventy-seven patients with nonmetastatic ES of the pelvis were treated at Rizzoli Institute between 1979 and 1996. Four different protocols of chemotherapy were used successively. Two protocols consisted of VACAc, and two of VACAc plus ifosfamide and etoposide. Local treatment consisted of surgery in 5 patients, radiotherapy in 60, and surgery followed by radiotherapy in 12. Mean follow-up was 11 years (range 5-25 years). Thirty-three patients remained continuously free of disease; 43 relapsed (24 due to metastases and 19 to local recurrence and metastases); 1 died of treatment-related complications. The 5- and 10-year event-free survival rates were 45% and 44%, respectively, and the 5- and 10-year overall survival rates were 48 and 44. These results are significantly worse than the ones achieved in 329 contemporary patients with extrapelvic lesions treated with the same protocols of chemotherapy (5- and 10-year event-free survival = 46% vs. 64% and 44% vs. 69%). Thus, despite associated chemotherapy, the outcome of ES localized in the pelvis remains poor, and new innovative methods for the treatment of this tumor are needed.     

An analysis of primary site control and late effects according to local control modality in non-metastatic Ewing sarcoma

PURPOSE: To examine prognostic factors for primary site control and analyze late effects according to local treatment modality in non-metastatic Ewing sarcoma (ES). MATERIALS AND METHODS: From 1976 to 2001, 76 patients with localized ES and a median age of 14.5 years were seen and treated at one institution. Tumors were located in the extremity in 38, pelvis in 13, spine in 11, trunk in 8, and head and neck in 6. Tumor size was < or = 8 cm in 44 and >8 cm in 32. Local therapy included radiotherapy (RT) alone in 40, surgery (S) alone in 27, and surgery followed by postoperative radiotherapy (S + RT) in 9. Chemotherapy (CT) was delivered to 65 patients (86%). Median follow-up for surviving patients was 9.7 years. RESULTS: The 5- and 10-year overall survival rates were 57.5% and 52.1% while the 5- and 10-year local control rate was 79.2%. The 5- and 10-year local control rates were 78.2% for RT, 77.6% for surgery, and 88.9% for S + RT (P = 0.68). Multivariate analysis showed that only the use of CT was found to be a prognostic factor for local control (P = 0.014). The 5- and 10-year local control rates were 83.7% for those receiving CT and 51.1% for those not receiving CT. For patients followed at least 5 years from diagnosis, late effects were seen in 10 of 19 (52.6%) receiving RT, 2 of 5 (40%) receiving S + RT, and 4 of 16 (25%) receiving surgery alone. The most common late effects with RT were muscular atrophy, limb length growth delay, and development of second malignancy. Scoliosis and decrease range of motion of an extremity were seen regardless of local treatment modality. Three patients who had surgery alone had an amputation whereas two who had RT had an amputation secondary to relapse or development of osteosarcoma. CONCLUSION: In this single institution study, the use of CT was the only factor found to impact on local control. Late effects were common regardless of local control strategy.     

儿童朗格罕斯细胞组织细胞增生症34例临床分析

目的探讨儿童朗格罕斯细胞组织细胞增生症(LCH)的临床特点和预后,以期提高LCH诊疗水平。方法对34例初发LCH儿童患者进行回顾性分析。结果 34例患者中位年龄14.5个月(22 d至60个月),其中0~2岁的23例、2岁的11例;高危组17例,低危组17例。30例患者接受化疗,6周化疗总有效率67%(20/30),12个月总有效率87%(26/30),3年总生存(OS)率为86%±6%,3年无事件生存(EFS)率为64%±9%。高危组患者6周化疗有效率46.7%,3年OS为72%±12%,3年EFS为46%±13%,均低于低危组(86.7%、100%、82%±9%),差异均有统计学意义(P0.05)。高危组12个月化疗有效率(80%)与低危组(93%)的差异无统计学意义(P0.05);复发率和死亡率均为27%,而低危组无复发和死亡。结论 LCH总体生存率较高,但高危组6周化疗有效率低,远期预后较差。     

Clinical outcome in children with craniopharyngioma treated with primary surgery and radiotherapy deferred until relapse

BACKGROUND: To report the clinical outcome in children with craniopharyngioma following primary surgery and deferred radiotherapy at relapse. PROCEDURE: Twenty-five children with craniopharyngioma were treated with primary surgery. Total resection was achieved in 19 children (76%), while in 24% total resection was not achieved due to tumor adhesion to adjacent critical structures. None of these children received radiation therapy immediately after total or sub-total resection. Radiotherapy was delivered at the time of relapse in 11 patients (44%). RESULTS: The median follow-up from primary surgery was 10 years (3-16 years). The 14 year overall survival was 100%. Tumor recurrence was observed in (12/25) 48% at a median interval of 17 months. Tumor recurrence following total resection was 6/19 (32%) compared to 100% (6/6) following sub-total resection, and radiotherapy. The 2, 3, and 6 years relapse-free survival following initial surgery was 72, 55, and 50%, respectively. Univariate analysis revealed only extent of surgery to be significant for local recurrence (P < 0.0001). The sequelae observed in these patients included panhypopituitarism (100%), appetite disorders and hypothalamic obesity (32%), neuropsychological and behavioral disorders (20%), and sleep disorders (12%). Majority of children with non-endocrine complications had a local recurrence requiring further surgery and radiotherapy. CONCLUSIONS: The two standard treatment options in children with craniopharyngioma are primary surgery and sub-total resection followed by radiotherapy. In certain subgroups of patients such as those with large tumors and hypothalamic extension, primary surgery is associated with a high incidence of complications and high failure rates. We recommend utilization of an individualized risk-based treatment approach, that attempts to maximize cure rates without compromising long-term functional outcome in children with craniopharyngiomas.     

儿童伯基特淋巴瘤62例临床特征及预后分析北大核心CSCD

目的分析儿童伯基特淋巴瘤(Burkitt’s lymphoma,BL)的临床特点、化疗疗效,以及利妥昔单抗治疗对BL患儿预后的影响。方法回顾性收集62例BL患儿的临床资料,对BL患儿的临床特点、疗效及预后相关因素进行分析,采用Cox回归分析BL患儿预后不良的相关因素。根据是否应用利妥昔单抗治疗将晚期(Ⅲ/Ⅳ期)BL患儿分为化疗联合利妥昔单抗组和单纯化疗组,比较两组预后情况。结果62例患儿发病时中位年龄5(范围1~14)岁,男58例(94%),女4例(6%)。原发部位为腹腔者41例(66%),头颈部者16例(26%)。Ⅰ、Ⅱ、Ⅲ、Ⅳ期患儿分别为1例(2%)、8例(13%)、33例(53%)、20例(32%)。中位随访时间29个月,进展/复发患儿15例(24%),3年总生存率、无事件生存率分别为82.8%±5.2%、77.3%±5.8%。Ⅲ/Ⅳ期患儿中,化疗联合利妥昔单抗组(n=16)与单纯化疗组(n=30)3年总生存率分别为93.3%±6.4%、65.6%±9.9%,差异有统计学意义(P=0.042);3年无事件生存率分别为86.2%±9.1%、61.8%±10.1%,差异无统计学意义(P>0.05)。Cox回归分析结果显示:中枢神经系统侵犯、乳酸脱氢酶水平>1000 U/L、早期未完全缓解为BL患儿预后不良的相关因素(P<0.05)。结论化疗联合利妥昔单抗治疗能改善Ⅲ、Ⅳ期BL患儿预后;中枢神经系统侵犯、乳酸脱氢酶水平升高、早期未完全缓解可能提示BL患儿预后不良。     

Poor prognosis infantile fibrosarcoma with pathologic features of malignant fibrous histiocytoma after local recurrence

In a retrospective study of infants under 1 year of age treated at our institution over a 30-year period for soft tissue tumors, eight fibrosarcomas (FS) were seen, six of which were congenital. Therapy consisted of local excision (n = 3), radiotherapy (n = 1), surgery + radiotherapy (n = 1), surgery + chemotherapy (n = 1), and surgery + chemotherapy + radiotherapy (n = 2). Among these eight patients, four are alive in first complete remission (CR) with 13, 17, 23, and 27 years of follow-up. Of the remaining four patients, two had local recurrences and are still alive in CR after re-excision of the tumor, while the other two had both local and distant relapses and died. Interestingly, in the two patients who developed distant metastases, the pathologic pattern was that of malignant fibrous histiocytoma (MFH) at the time of local recurrence. To our knowledge, no similar cases of transitions between infantile FS known for its favorable outcome and MFH have been reported in this age group. The relevance of such transitions is difficult to assess. However, given the known metastatic potential of MFH, we believe that chemotherapy regimens currently used in the management of childhood soft tissue sarcomas should be used in similar cases.     

Malignant germ cell tumors in childhood: results of the first Italian cooperative study "TCG 91"

BACKGROUND AND AIMS: About 20% of patients with germ cell tumor (GCT) are still resistant to therapy. To investigate which features are present in resistant patients, a multicenter study on GCT in children was undertaken to correlate clinical and laboratory parameters with the outcome. METHODS: Patients aged less than 16 years, with histologically proven extracranial GCT were included. RESULTS: Ninety-five patients (median age 33 months, 45 males) were eligible. The site of the primary tumor was gonadal in 59, extragonadal in 36. The stage was I in 39; II in 5; IIIa (microscopic residue) in 7; IIIb (macroscopic residue) in 16; IIIc (unresectable) in 13; IV in 15. The treatment was surgery alone in 31; surgery plus radiotherapy in 1; chemotherapy +/- surgery in 63. Post-chemotherapy resection in 19 (10 complete, 9 partial). The chemotherapy regimen was carboplatin 400 mg/m2/day on days 1, 2; etoposide 150 mg/m2/day on days 1, 2; ifosfamide 1,500 mg/m2/day on days 21, 22; dactinomycin 1.5 mg/m2/day on day 21; vincristine 1.5 mg/m2/day on day 21. Three patients died because of toxicity and two non-responders (to primary chemotherapy), died of progression; among the remaining 90 patients 20 relapsed, 9 are in second remission, 2 are alive with disease, and 9 died of disease progression (one from progression and intracranial hemorrhage). Overall survival was 82.7% and event-free survival: 71.5%. Survival according to: (a) site: testis: 100%; ovary: 88%; sacrococcyx: 69.6%; other sites: 33.3% (P < 0.001); (b) stage: I and II: 100%; IIIa: 83.3%; IIIb: 84.6%; IIIc: 60.6%; IV: 53.2% (P < 0.001); (c) AFP levels: normal: 85.5%; 42-9,470 ng/ml: 84.6%; >/=10,000 ng/ml: 58.7% (P = 0.02). All the pts who had complete resection of the primary tumor at diagnosis or at delayed surgery, remained in remission. CONCLUSIONS: Multivariate analysis showed that the primary site of tumor was the only independent prognostic factor for survival and EFS.     

Efficacy of Preoperative Chemotherapy in Treatment of Children With Wilms’ Tumor: A Meta-Analysis

Context:

To assess the efficacy of preoperative chemotherapy in Wilms’ tumor patients and explore its true value for specific subgroups.

Objectives:

In the presence of these controversies, a meta-analysis that examines the efficacy of preoperative chemotherapy in Wilms’ tumor patients and specific subgroups is needed to clarify these issues. The objective of this meta-analysis is to assess the efficacy of preoperative chemotherapy in Wilms’ tumor patients and explore its true value for specific subgroups.

Data Sources:

Computer-based systematic search with “preoperative chemotherapy”, “Neoadjuvant Therapy” and “Wilms’ tumor” as search terms till January 2013 was performed.

Study Selection:

No language restrictions were applied. Searches were limited to randomized clinical trials (RCTs) or retrospective studies in human participants under 18 years. A manual examination of references in selected articles was also performed.

Data Extraction:

Relative Risk (RR) and their 95% Confidence Interval (CI) for Tumor Shrinkage (TS), total Tumor Resection (TR), Event-Free Survival (EFS) and details of subgroup analysis were extracted. Meta-analysis was carried out with the help of the software STATA 11.0. Finally, four original Randomized Clinical Trials (RCTs) and 28 retrospective studies with 2375 patients were included.

Results:

For preoperative chemotherapy vs. up-front surgery (PC vs. SU) group, the pooled RR was 9.109 for TS (95% CI: 5.109 - 16.241; P < 0.001), 1.291 for TR (95% CI: 1.124 - 1.483; P < 0.001) and 1.101 for EFS (95% CI: 0.980 - 1.238; P = 0.106). For subgroup short course vs. long course (SC vs. LC), the pooled RR was 1.097 for TS (95% CI: 0.784 - 1.563; P = 0.587), 1.197 for TR (95% CI: 0.960 - 1.493; P = 0.110) and 1.006 for EFS (95% CI: 0.910 - 1.250; P = 0.430).

Conclusions:

Short course preoperative chemotherapy is as effective as long course and preoperative chemotherapy only benefits Wilms’ tumor patients in tumor shrinkage and resection but not event-free survival.